2-trichloromethyl-4-thiazolidones



United States Patent 3,270,027 2-TRICHLOROMETHYL-4-THIAZOLIDONES Alexander R. Surrey, Albany, N.Y., assignor to Sterling Drug Inc., New York, N.Y., a corporation of Delaware No Drawing. Filed Oct. 15, 1963, Ser. No. 316,470 4 Claims. (Cl. 260-301) This inveniton relates to compounds of the class of 4-thiazolidones.

The invention resides in the concept of chemical compounds having the structural Formula I where R is hydrogen or lower-alkyl, and Z is S-, SO or 80 The term lower alkyl, as used herein, e.g., as one of the meanings for R in Formula I, means alkyl radicals having from one to six carbon atoms and is illustrated by methyl, ethyl, u-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, n-amyl, isoamyl, n-hexyl, 3-hexyl, and the like.

The 2-trichloromethyl-4-thiazolidones of Formula I where Z is -S were prepared by heating a mixture of chloral hydrate, a 2-mercaptoal kanoic acid and ammonia or an ammonium salt that produces ammonia on heating. The preferred method was by heating in an inert solvent, such as dioxane, benzene or pyridine, -a mixture of ammonium carbonate or ammonium acetate, a 2-mercaptoalkanoic acid having the formula HSC-HRCOO'H, and chloral hydrate, where R is lower-alkyl. Instead of ammonium carbonate or ammonium acetate, other salts of ammonia, preferably those with weak inorganic or organic acids that decompose readily when heated to produce ammonia can be used.- Alternatively, ammonia can be used directly, for example, a solution of ammonia in methanol was found to produce satisfactory results. Still another procedure that can be used is the heating of chloral hydrate with the ammonium salt of said Z-mercaptoalkanoic acid. The foregoing procedures are carried out preferably in anhydrous medium, and with a continuous separator connected to the apparatus to remove water as it is formed by the reaction. However, use of the anhydrous conditions and the continuous separator is not necessary since the reaction will proceed in the presence of water, although the yield may be less in some instances.

The 2-trichlor0methyl-4-thiazolidone-l-oxides of Formula I where Z is SO are prepared by oxidizing the corresponding trichloromethyl-4-thiazolidones. tion is carried out by reacting the 4-thiazolidone with an oxidizing agent effective to oxidize sulfides to sulfoxides. Various oxidative procedures can be employed but the one preferred in practicing my invention comprises using a per-organic acid, e.g., peracetic acid, in a suitable solvent, e.-g., ethyl acetate. The reaction is exothermic and is carried out preferably by mixing the reactants at a low temperature, i.e., from 0 C. to C. Other oxidizing agents that can be used are other perorganic acids, e.g., perbenzoic acid.

The 2-trich1oromethyl-4-thiazolidone 1,1 dioxides of my invention (Formula I where Z is S0 are prepared preferably by oxidizing the corresponding 2-trichloromethyl-4-thiazolidones (Formula I where Z is S). This oxidation is carried out by reacting the 4-thiazolidone with an oxidizing agent effective to oxidize sulfides to sulfones. Various oxidative procedures can be employed, but the one preferred in practicing my invention comprises using potassium permanganate in aqueous acetic acid solution. Other oxidizing agents that can be used include hydrogen peroxide, chromium trioxide (CrO and the like. Also, the oxidation can be carried out using an excess of perorganic acid, e.g., peracetic acid, at about This oxidaroom temperature (20-25 C.) for several days. Alternatively, the 2-trichloromethyl-4-thiazolidone-1,l-dioxides can be prepared by oxidizing the corresponding l-oxides (Formula I where Z is SO), using these same oxidizing agents effective to oxidize sulfides to sulfones, e.g., potassium permanganate, hydrogen peroxide, etc.

The chemical structures of my 2-trichloromethyl-4- thiazolidones and corresponding l-oxides and -1,1-dioxides are established by the mode of their syntheses and corroborated by the correspondence of calculated and found values for the elementary analyses for representative examples.

The compounds of my invention have been tested by standard herbicidal evaluation procedures and found to have selective herbicidal activity against various noxious weeds, e.g., crabgrass, chickweed, curled dock, wild oats and pigweed, while having no activity against certain crops, e.g., corn, at the same application levels.

The following examples will further illustrate specific embodiments of the invention without, however, limiting it thereto.

Example I Z-trichloromethyl-4-thiazolidone was prepared using ammonium acetate as the source of ammonia as follows: To a solution containing 66 g. of chloral hydrate and 300 cc. of dioxane was added a solution containing 30 cc. of thioglycolic acid and 33 g. of ammonium acetate whereupon the temperature rose from 30 to 35 C. and dissolution resulted. The reaction mixture was then heated on a steam bath under reflux for six-teen hours, cooled and filtered. The solid that was filtered oif was washed with diox-ane and ether and the washings were combined with the filtrate. The filtrate and washings were evaporated in vacuo to yield a residue which soliditied on standing. The solid residue was broken up and shaken thoroughly with a small amount of ether (about 50 ml.) and about 300 cc. of water containing 30 cc. of concentrated ammonium hydroxide. The solid product was collected to yield 33 g. (37.5%) of 2-trichloromethyl-4-thiazolidone, MJP. 155158 C. The product was recrystallized from 250 cc. of benzene using decolorizing charcoal to yield 24 g. of the product, M.P. 161- 163 C. These 24 g. were combined with 8 g. of the product obtained using ammonia dissolved in methanol (preparation given below) and recrystallized from approximately 200 cc. of ethyl alcohol using decolorizing charcoal. There was thus obtained 22.3 g. of 2-trichloromethyl-4-thiazolidone. After drying for sixteen hours at C., it melted at 166467 C. (corr.) with decomposition.

An-alysis.-Calcd. for C H Cl NOS: Cl, 48.24; S, 14.54. Found: Cl, 48.07; S, 14.73.

Following the above procedure but using in place of thioglycolic acid molar equivalent quantities of Z-mercaptopropionic acid, 2-mercaptobutanoic acid and Z-mercaptohexanoic acid, there are obtained, respectively, S-methyl 2-trichloromethyl-4-thiazolidone, S-ethyl-Z-trichloromethyl-4-thiazolidone and 5-n-butyl-2-trichloromethyl-4- thiazolidone.

2-trichloromethyl-4-thiazol-idone was prepared using a solution of ammonia in methanol as follows: A mixture containing 33 g. of chloral hydrate, 15 cc. of thioglycolic acid, 300 cc. of dry benzene and 35 cc. of ammoniacal methanol (10% NH was refluxed with a continuous separator connected to the reaction vessel for removal of water formed by the reaction. After one hour, 10 cc. of water had been collected and after fifteen hours, a total of only 11 cc. had been collected. The reaction mixture was cooled and the solid that separated was collected and shaken thoroughly with water containing 15 cc. of concentrated ammonium hydroxide and filtered. The residue was washed with water and ether to yield 7.5 g. of the product, M.P. 160 C. The ether layer of the filtrate was separated from the aqueous layer, dried over anhydrous magnesium sulfate, treated with decolorizing charcoal, filtered and evaporated to yield 2.5 g. of white solid, M.P. 151-155 C. The combined 9.8 g. of the product was recrystallized from about 125 cc. of benzene using 4 had a corrected melting point of l78.2179.8 C. with decomposition.

Analysis.Calcd. for C H CI NO S: N, 5.92; S, 13.53. Found: N, 6.18; S, 13.60.

Following the above procedure but using molar equivalent quantities of 5-methy1-, 5-ethylor 5-n-butyl-2-trichloromethyl-4-thiazolidone in place of 2-trichloromethyl- 4-thiazolidone, there are obtained, respectively, 5-methyl-, S-ethylor S-n-butyl-2-trichloromethyl-4-thiazolidone-1- oxide.

decolorizing charcoal to yield 8 g. of the product, 2-tri- 10 Example 3 eh10r0methyl-4-thiaZOlidOHe, which was dried at 95 2-trichloromethyl-4-thiazolidone-1,l-dioxide was prefor four hours and found to m l t As pared as follows: To a stirred solution containing 27 g. of noted above, these 8 of the Preduet were recrystallized 2-trichloromethyl-4-thiazolidone dissolved in 100 cc. of together with the Product Obtained y the above p glacial acetic acid and kept at about 15-20" C. was added ure using ammonium aeetate as the source of ammoniaa solution containing 28 g. of potassium permanganate in 2-trlehl0r01hethyl-4-thlaZ0lid0rle was also P p 800 cc. of water. The reaction mixture was decolorized ing ammonium carbonate as the source of ammonia as folby ddi an aqueous olution of sodium bisulfite. The lows! A mixture Containing of chloral y solution was allowed to stand in a refrigerator and the 7-2 2- f ammonium carbonate, 0 f i ne nd solid that separated was collected and recrystallized from cc. of thloglyeolle acid was heated 011 a Steam hath 400 cc. of benzene using decolorizing charcoal to yield with stirring overnight (about fifteen hours). The re- 11.5 g. of the product, 2-trichloromethyl-4-thiazolidoneaction mixture was decanted from a small amount of solid l,l dio id M P, 162 5-163.4 C. (mm). and evaporated in vacuo to remove the solvent. The Analysis.-Calcd. for C H CI NO S: N, 5.55; S, 12.70. residual oily material was dissolved in ether. The ether Found: N, 5.63; S, 12.82. solution was washed with water containing ammonium Following th b ve procedure but using molar equivhydroxide solution and evaporated to dryness. The resialent quantities of 5-methyl-, S-ethylor 5-n-butyl-2-tri due was heated with benzene until no more wa r w r chloromethyl-4-thiazolidone in place of 2trichloromethmoved azeotropically. The benzene solution was treated l-4-thiazolidone, there are obtained, respectively, 5-methwith decolorizing charcoal, filtered, and to the hot filtrate yl-, S-ethylor 5-n-butyl-2-trichloromethyl-4-thiazolidonewas added n-hexane. The solid that separated was col- 1,l-dioxide leeted to yield of 2-trlehl0r0methy1-4-thlaZ0lid0I1e, The herbicidal activity of my compounds is illustrated M.P. 157160 C. Another 15 gf Z-tIiCh YI- by the following results obtained from both pre-emergent 4-thiazolidone, M.P. 155-159 C. was obtained by addiand post-emergent applications. tion of more hexane to the above filtrate. The total of The results presented in Table A were obtained using 6.0 g. of product was used in Example 2. acetone solutions of 2-trichloromethyl-4-thiazolidone Example 2 (Example 1) and 2-trichloromethyl-4-thiazolidone-1,1- dioxide (Example 3), and applying the solutions to greenz'trlehloromethyl-4'thlalelldohe-ljolrlde Was P e house flats containing the freshly planted seeds of various as follows- To suspenswn eohtalhlhg of 4 species (for pre-emergence) or to greenhouse flats conchloromethyl-4-th1azolldone and 50 cc. of benzene chilled mining two to three k 1 plants (f poshemergehce; to C was added: f W1rling, Solution containing two week old plants in the summer and three week old 5.7 g. of 40% peraceuc acid dissolved in 50 cc. of ethyl plants in the winter) Samples of 200 100 50 and 25 acetate also ehllled The temperature Q t0 mg. of compound per 10 cc. of solvent were used for pre- 20 C. and dissolution resulted. The reaction mixture emergence, the quantities f Compound b i equivalent was cooled again to 4 C. and then allowed to stand at to 1 8, 4 and 2 1 per acre, respectively Th post. P temperature for tyh hours- The reaction emergent application was equivalent to 8 lbs. of compound mixture was washed successively with aqueous sodium biper acre" Samples f the compounds were li d to com sulfite solution and water, and then evaporated in vacuo and the listed d d i observations d i j to remove the solvent. The resulting solid was recrystalratings were d 2 to 3 weeks after lj ti llZed from ethylene dichloride to yield of the P and 7 to 10 days after post-application. Further obseruct, 2-trichloromethyl-4-thiazolidone-l-oxide, MP. 179- vation was made as dictated by effects from treatment. 181 C. A sample recrystallized from isopropyl alcohol The injury rating scale used was as follows:

TABLE A Example 1 Example 3 Pounds per acre Pounds per acre Plant specie Pre Post Pre Post 2 4 s 16 s 2 4 s 16 8 Corn 0 0 0 2 0 0 0 1 3 2 Wild Oats 2 3 a a 1+ 2 3 4 3 2 Client Grass 2 3 4 3 1 2+ 3 4 3 2 Foxtail 2 2 a 4 1 1 2 4 4 1 Barnyard Gras 1 2 2+ 3 1 1 2 3 3 Crabgrass l 2 4 4 1 3 4 4 4 3 Johnson Grass 1 2 4 4 1+ 1 2 2+ 3 2 Yellow Rocket..." 2 3 4 4 1+ 1 2 3 3 3 ChickweetL... 4 4 4 4 1+ 4 4 4 4 3 Pigweed 3 3 4 4 2 0 1 4 4 3+ Velvet Leaf- 1 1+ 3 4 1 0 1 1 1 2 Lambsquart 2 2+ 3+ 4 3 1 3 3 4 4 Curled Dock 3 4 4 4 a 1 3 3 4 4 3Severe injury.

4Death (all plants killed).

The above data show the selective control of various Weeds, e.g., crabgrass, chickweed, curled dock, etc., in plantings of corn.

The results lfor 2-trichloromethyl-4-thiazolidone-loxide (Example 2) in Table B were obtained as above but using only a 16 lb./acre pre-emergent application and using a different injury rating scale, i.e., from O to 10, with representing no injury; 10 representing 100% injury (all plants killed); and, 1 to 9 representing from 10 to 90% in ury.

TABLE B Example 2 Plant specie Pre Post 16 lbs/acre 8 lbs/acre 6 0 3 6 7 0 0 2 0 5 0 Johnson Grass 1 0 Yellow Rocket. 1 1 Ghiekweed. 2 2 Pigweed. 10 6 Velvet Leaf 1 2 Lambsquarter 10 1 Curled Dock 5 0 On the basis of the quantities of compound used, the above data show the selective control of certain weeds, e.g., wild oats, pigweed, in plantings of corn using postemergent application of the compound.

The compounds of my invention are prepared for herbicidal application by admixing a compound of the invention, e.g., 2-trichlorornethyl-4-thiazolidone, with herbicidal adjuvant as carrier to provide compositions in liquid or solid form. Liquid compositions are prepared by admixing an active compound with conventional liquid diluent media; since the compounds are relatively insoluble in water, they are conveniently prepared in common organic solvents, e.g., acetone, ethanol, etc., or in where R is a member selected from the group consisting of hydrogen and lower-alkyl, and Z is a member selected from the group consisting of S, and

2. 2-trichloromethyl-4-thiazolidone.

3. 2-trichloromethyl-4-thiazolidone-l-oxide.

4. 2-trichloro'methyl-4-thiazolidone-1,1-dioxide.

References Cited by the Examiner UNITED STATES PATENTS 2,647,905 8/1953 Surrey 260-301 2,915,527 12/1959 Campbell et al. 260307.3 2,973,366 2/1961 Bimber 260307.3

OTHER REFERENCES Bishop et al.: J. Chem. Soc. (London), 1963, pages 23812385.

Burger: Medicinal Chemistry (New York, 1960), pages 77-81.

HENRY R. JILES, Acting Primary Examiner.

NICHOLAS S. RIZZO, Examiner.

A. D. ROLLINS, Assistant Examiner. 

1. A COMPOUND OF THE FORMULA 